Therapeutic agents such as peptides and low molecular weight proteins used in the treatment of diseases suffer from significant limitations. These agents are often eliminated by the kidneys within a short period of time or are destroyed by proteases therefore limiting their bioavailability, resulting in short plasma half-life and lower drug concentrations than are required to be efficacious. A high clearance of a therapeutic agent is not optimal in cases where it is desired to maintain a high serum level over an extended period of time to obtain maximal efficacy. Increased doses or increased frequency of administration often result in a higher therapeutic efficacy but a higher risk of side effects as well, limiting the dose or frequency that can be administered.
Many peptide hormones have extremely short half-lives in the bloodstream, resulting in the loss of biological activity not long after administration. Gastrin is a peptide hormone that has been shown in combination with other growth factors to be efficacious in the treatment of diabetes. However, when gastrin is administered alone, there is only limited efficacy. In addition, it has been found that gastrin has a relatively short half life. Gastrin-17 for instance has a circulating half-life of about 5-9 mins while gastrin-34 has a circulating half-life of about 35 mins.
There is a need for compositions containing gastrin compounds that have a protracted or long-acting action.